The University of Southampton
University of Southampton Institutional Repository

Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome
Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome
BACKGROUND: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes.

METHODS: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates.

RESULTS: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined.

CONCLUSIONS: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies.

IMPACT: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.
987-992
White, K.L.
ba20bd50-69e1-4980-8099-9fbb382e3f7d
Vierkant, R.A.
840e4bba-e431-4e17-aef9-fca11cf9c1c3
Fogarty, Z.C.
e68c5e17-10c1-4449-b3ab-528dd84a1431
Charbonneau, B.
5fb5e83b-1373-4aa7-86f9-f7e892de770d
Block, M.S.
8c2d7bdf-d5f4-42f0-a458-cccb9f0864e2
Pharoah, P.D.P.
72233519-0a97-430d-9b68-267585ca7cb7
Chenevix-Trench, G.
e90da721-7c34-4695-902f-34496a53526f
Rossing, M.A.
99d3b2d7-c9b0-4c87-9a81-e916cb180c95
Cramer, D.W.
8a1329b4-cfe6-4ddf-a5cc-8da483615226
Pearce, C.L.
ccc2ec44-edf2-4851-be8f-89310bcceabc
Schildkraut, J.M.
809ac658-f4e1-47be-9dbc-8a14cfc20e06
Menon, U.
9b09d647-03b2-40fd-bf7f-150e7ebcb10f
Kjaer, S.K.
9ef7bf1d-5017-4f15-b10f-abe8b0d1a7bf
Levine, D.A.
150a09fa-a9d5-464e-8ee7-913c83baf88f
Gronwald, J.
ea39599c-3dcd-4558-9a25-d19c6bbf0355
Culver, H.A.
e4f3010e-246b-449a-9e01-9e1d2c55ce66
Whittemore, A.S.
ba7e60b8-0afa-4f20-857d-a40ca86e4623
Karlan, B.Y.
226988d5-e1b5-426b-b461-6890455cf6bf
Lambrechts, D.
0f6f53b4-8e06-4003-946f-23a7c1794d54
Wentzensen, N.
00059d06-23c5-46ba-b566-dba69c93d07c
Kupryjanczyk, J.
0e37f951-67fd-46b3-b2ea-56a04e56114e
Chang-Claude, J.
148388a1-b116-4ebd-9d4a-190975ed0cfd
Bandera, E.V.
8486e0f9-b736-44b1-9584-03cbe153f700
Hogdall, E.
d281e03d-0b98-4f7d-a8a0-7f1d1a932323
Heitz, F.
e583e44b-497c-4fa2-b022-52e11d6774ab
Kaye, S.B.
00f3cf34-72be-494a-bd9b-e10b67d19f0f
Fasching, P.A.
27eebdb3-353a-435d-8859-c7d9002a0ef2
Campbell, I.
e6743f56-fcae-4a90-8182-b1cdd39362d0
Goodman, M.T.
e5310c38-1330-4b1e-bb47-b375247a7486
Pejovic, T.
9eca0f54-2ddc-4ebe-b932-d6ff4fdb14f1
Bean, Y.
cf148f0d-ade1-4922-8bf0-dc4b23e3ce6e
Lurie, G.
e9368821-abb4-4054-ae58-6b88f6645988
Eccles, D.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Hein, A.
124afe6a-81e8-48b7-84cc-397962768cc0
Beckmann, M.W.
259c55a8-0ea1-42a9-abc2-514fc0a1ad25
Ekici, A.B.
44ca45c0-3a86-4a3d-9266-ef6c2b3007d3
Paul, J.
fb875029-2055-41f1-a8a6-db8cfa05f5e9
Brown, R.
b9108870-6092-4963-b323-be7254c71976
Flanagan, J.M.
8e349519-4bf2-42a6-8650-ff950f2a14a9
Harter, P.
276e1f1f-0082-4f0a-9951-2624fe50cbae
du Bois, A.
455c7665-9c65-447d-9626-b5d18152bc03
Schwaab, I.
0c914b1d-5451-4ac5-9162-b6518099df53
Hogdall, C.K.
df0a9d65-432a-42af-b8b4-e28c015fafff
Lundvall, L.
d5068a9f-eefc-4c47-934b-ad4a7a905d41
Olson, S.H.
85dfc640-81eb-42f2-a5ac-4de56aadc5d5
Orlow, I.
440ec630-9b1a-4333-bc32-3252a01a982b
Paddock, L.E.
745e7b0d-1533-41f7-b52c-ba9e4ac79676
Rudolph, A.
b34e2172-6abe-4c75-9dd5-8c1909e5ecc4
Eilber, U.
80958851-de64-4efd-88e4-1f261d02f066
Dansonka-Mieszkowska, A.
fc8db4ee-7c5f-442c-ab27-351488fda028
Rzepecka, I.K.
a182e4fb-08c1-4e93-b937-5e92c8a9a81a
Ziolkowska-Seta, I.
cf51204c-5a9f-4359-9594-0f7c53357c91
Brinton, L.
dbd1c4c4-ad4e-4c0c-8d48-d0fdf66b23b6
Yang, H.
c0c036ca-374c-4c71-84a5-89ce439a7e3e
Garcia-Closas, M.
353b0a3c-e5dd-4a43-bd35-b22f6929cc58
Despierre, E.
891387ee-26fb-482d-80fa-4eca1df11a13
Lambrechts, S.
5c20f6a9-fbca-42bb-a63f-6b5213a9dbdc
Vergote, I.
438114fc-bce7-4e4a-9976-6745c589ea50
Walsh, C.
000b0eb1-ba84-44ad-a8ee-8e0f1ea87397
Lester, J.
37d845f6-1d28-4b2b-8535-b938a491396e
Sieh, W.
336a5bac-06d8-452a-8b89-181bcb5f20c8
McGuire, V.
327b70d0-675f-48dd-99c5-01f84ebe2dc4
Rothstein, J.H.
6356a102-f70d-4625-9520-f69055be4b2a
Ziogas, A.
807fa7a0-ed7a-4305-be9b-9c46a33cefa9
Lubinski, J.
63a971db-39b7-4e5a-a932-8a8c645ea72f
Cybulski, C.
f63a16af-2625-4ae3-996e-44de1b34aa9a
Menkiszak, J.
c59e036c-dfbd-4364-9a96-ffae04e961c3
Jensen, A.
0d572625-131e-41d5-a3b5-65f8382a5f36
Gayther, S.A.
08ec2b68-2561-42ed-a3c6-1a71cf37c93e
Ramus, S.J.
af8ce21a-1dec-4da4-a8ea-3da51e666ef6
Gentry-Maharaj, A.
df8f0fdd-d109-4712-a323-456c686e633e
Berchuck, A.
b847c144-e69d-4e67-8f45-45a172642582
Wu, A.H.
bb7a2a17-e033-48ac-af08-7091f4668683
Pike, M.C.
49051310-4a7d-4f40-8048-d2e8add6564a
Van DenBerg, D.
95b843c5-ca9f-4fed-83fc-e7e30331f9ed
Terry, K.L.
e89f9dcb-cfb6-4c7b-a667-7fe744d6caa4
Vitonis, A.F.
700fd628-54a4-471e-856c-e582dc1880e7
Doherty, J.A.
d9a2a6d1-2c83-4f74-b063-d0d0c4bd2e29
Johnatty, S.E.
932cb1d8-5bfc-4f7e-87bc-c3e4b314b311
deFazio, A.
d48e7060-a665-4ab9-8ebb-93022fb230a8
Song, H.
80485532-eb2c-4613-8fb9-00bf2ce3fc11
Tyrer, J.
0df99982-ea75-479a-adb2-a2add0946ae6
Sellers, T.A.
62d802d7-baab-46e5-ac9d-e45b83775f1f
Phelan, C.M.
2e5e4d2f-54ea-4e3b-a7ab-0a951cb910bb
Kalli, K.R.
8bdfc2ae-9ad3-4351-939c-66cc596068bd
Cunningham, J.M.
7064cd6c-6574-40a2-9613-d2afb21a14c6
Fridley, B.L.
8e3ff47b-c084-458e-9116-cbcd8e50146a
Goode, E.L.
0fc5f473-1989-4403-999e-2ec928659d3b
White, K.L.
ba20bd50-69e1-4980-8099-9fbb382e3f7d
Vierkant, R.A.
840e4bba-e431-4e17-aef9-fca11cf9c1c3
Fogarty, Z.C.
e68c5e17-10c1-4449-b3ab-528dd84a1431
Charbonneau, B.
5fb5e83b-1373-4aa7-86f9-f7e892de770d
Block, M.S.
8c2d7bdf-d5f4-42f0-a458-cccb9f0864e2
Pharoah, P.D.P.
72233519-0a97-430d-9b68-267585ca7cb7
Chenevix-Trench, G.
e90da721-7c34-4695-902f-34496a53526f
Rossing, M.A.
99d3b2d7-c9b0-4c87-9a81-e916cb180c95
Cramer, D.W.
8a1329b4-cfe6-4ddf-a5cc-8da483615226
Pearce, C.L.
ccc2ec44-edf2-4851-be8f-89310bcceabc
Schildkraut, J.M.
809ac658-f4e1-47be-9dbc-8a14cfc20e06
Menon, U.
9b09d647-03b2-40fd-bf7f-150e7ebcb10f
Kjaer, S.K.
9ef7bf1d-5017-4f15-b10f-abe8b0d1a7bf
Levine, D.A.
150a09fa-a9d5-464e-8ee7-913c83baf88f
Gronwald, J.
ea39599c-3dcd-4558-9a25-d19c6bbf0355
Culver, H.A.
e4f3010e-246b-449a-9e01-9e1d2c55ce66
Whittemore, A.S.
ba7e60b8-0afa-4f20-857d-a40ca86e4623
Karlan, B.Y.
226988d5-e1b5-426b-b461-6890455cf6bf
Lambrechts, D.
0f6f53b4-8e06-4003-946f-23a7c1794d54
Wentzensen, N.
00059d06-23c5-46ba-b566-dba69c93d07c
Kupryjanczyk, J.
0e37f951-67fd-46b3-b2ea-56a04e56114e
Chang-Claude, J.
148388a1-b116-4ebd-9d4a-190975ed0cfd
Bandera, E.V.
8486e0f9-b736-44b1-9584-03cbe153f700
Hogdall, E.
d281e03d-0b98-4f7d-a8a0-7f1d1a932323
Heitz, F.
e583e44b-497c-4fa2-b022-52e11d6774ab
Kaye, S.B.
00f3cf34-72be-494a-bd9b-e10b67d19f0f
Fasching, P.A.
27eebdb3-353a-435d-8859-c7d9002a0ef2
Campbell, I.
e6743f56-fcae-4a90-8182-b1cdd39362d0
Goodman, M.T.
e5310c38-1330-4b1e-bb47-b375247a7486
Pejovic, T.
9eca0f54-2ddc-4ebe-b932-d6ff4fdb14f1
Bean, Y.
cf148f0d-ade1-4922-8bf0-dc4b23e3ce6e
Lurie, G.
e9368821-abb4-4054-ae58-6b88f6645988
Eccles, D.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Hein, A.
124afe6a-81e8-48b7-84cc-397962768cc0
Beckmann, M.W.
259c55a8-0ea1-42a9-abc2-514fc0a1ad25
Ekici, A.B.
44ca45c0-3a86-4a3d-9266-ef6c2b3007d3
Paul, J.
fb875029-2055-41f1-a8a6-db8cfa05f5e9
Brown, R.
b9108870-6092-4963-b323-be7254c71976
Flanagan, J.M.
8e349519-4bf2-42a6-8650-ff950f2a14a9
Harter, P.
276e1f1f-0082-4f0a-9951-2624fe50cbae
du Bois, A.
455c7665-9c65-447d-9626-b5d18152bc03
Schwaab, I.
0c914b1d-5451-4ac5-9162-b6518099df53
Hogdall, C.K.
df0a9d65-432a-42af-b8b4-e28c015fafff
Lundvall, L.
d5068a9f-eefc-4c47-934b-ad4a7a905d41
Olson, S.H.
85dfc640-81eb-42f2-a5ac-4de56aadc5d5
Orlow, I.
440ec630-9b1a-4333-bc32-3252a01a982b
Paddock, L.E.
745e7b0d-1533-41f7-b52c-ba9e4ac79676
Rudolph, A.
b34e2172-6abe-4c75-9dd5-8c1909e5ecc4
Eilber, U.
80958851-de64-4efd-88e4-1f261d02f066
Dansonka-Mieszkowska, A.
fc8db4ee-7c5f-442c-ab27-351488fda028
Rzepecka, I.K.
a182e4fb-08c1-4e93-b937-5e92c8a9a81a
Ziolkowska-Seta, I.
cf51204c-5a9f-4359-9594-0f7c53357c91
Brinton, L.
dbd1c4c4-ad4e-4c0c-8d48-d0fdf66b23b6
Yang, H.
c0c036ca-374c-4c71-84a5-89ce439a7e3e
Garcia-Closas, M.
353b0a3c-e5dd-4a43-bd35-b22f6929cc58
Despierre, E.
891387ee-26fb-482d-80fa-4eca1df11a13
Lambrechts, S.
5c20f6a9-fbca-42bb-a63f-6b5213a9dbdc
Vergote, I.
438114fc-bce7-4e4a-9976-6745c589ea50
Walsh, C.
000b0eb1-ba84-44ad-a8ee-8e0f1ea87397
Lester, J.
37d845f6-1d28-4b2b-8535-b938a491396e
Sieh, W.
336a5bac-06d8-452a-8b89-181bcb5f20c8
McGuire, V.
327b70d0-675f-48dd-99c5-01f84ebe2dc4
Rothstein, J.H.
6356a102-f70d-4625-9520-f69055be4b2a
Ziogas, A.
807fa7a0-ed7a-4305-be9b-9c46a33cefa9
Lubinski, J.
63a971db-39b7-4e5a-a932-8a8c645ea72f
Cybulski, C.
f63a16af-2625-4ae3-996e-44de1b34aa9a
Menkiszak, J.
c59e036c-dfbd-4364-9a96-ffae04e961c3
Jensen, A.
0d572625-131e-41d5-a3b5-65f8382a5f36
Gayther, S.A.
08ec2b68-2561-42ed-a3c6-1a71cf37c93e
Ramus, S.J.
af8ce21a-1dec-4da4-a8ea-3da51e666ef6
Gentry-Maharaj, A.
df8f0fdd-d109-4712-a323-456c686e633e
Berchuck, A.
b847c144-e69d-4e67-8f45-45a172642582
Wu, A.H.
bb7a2a17-e033-48ac-af08-7091f4668683
Pike, M.C.
49051310-4a7d-4f40-8048-d2e8add6564a
Van DenBerg, D.
95b843c5-ca9f-4fed-83fc-e7e30331f9ed
Terry, K.L.
e89f9dcb-cfb6-4c7b-a667-7fe744d6caa4
Vitonis, A.F.
700fd628-54a4-471e-856c-e582dc1880e7
Doherty, J.A.
d9a2a6d1-2c83-4f74-b063-d0d0c4bd2e29
Johnatty, S.E.
932cb1d8-5bfc-4f7e-87bc-c3e4b314b311
deFazio, A.
d48e7060-a665-4ab9-8ebb-93022fb230a8
Song, H.
80485532-eb2c-4613-8fb9-00bf2ce3fc11
Tyrer, J.
0df99982-ea75-479a-adb2-a2add0946ae6
Sellers, T.A.
62d802d7-baab-46e5-ac9d-e45b83775f1f
Phelan, C.M.
2e5e4d2f-54ea-4e3b-a7ab-0a951cb910bb
Kalli, K.R.
8bdfc2ae-9ad3-4351-939c-66cc596068bd
Cunningham, J.M.
7064cd6c-6574-40a2-9613-d2afb21a14c6
Fridley, B.L.
8e3ff47b-c084-458e-9116-cbcd8e50146a
Goode, E.L.
0fc5f473-1989-4403-999e-2ec928659d3b

White, K.L., Vierkant, R.A. and Fogarty, Z.C. et al. (2013) Analysis of over 10,000 cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome. Cancer Epidemiology, Biomarkers & Prevention, 22 (5), 987-992. (doi:10.1158/1055-9965.EPI-13-0028). (PMID:23513043)

Record type: Article

Abstract

BACKGROUND: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes.

METHODS: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates.

RESULTS: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined.

CONCLUSIONS: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies.

IMPACT: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.

This record has no associated files available for download.

More information

Accepted/In Press date: 6 March 2013
e-pub ahead of print date: 19 March 2013
Published date: May 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 382790
URI: http://eprints.soton.ac.uk/id/eprint/382790
PURE UUID: c5561c55-6964-4e32-83e5-ff8e1b57e710
ORCID for D. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 12 Oct 2015 14:34
Last modified: 15 Mar 2024 02:40

Export record

Altmetrics

Contributors

Author: K.L. White
Author: R.A. Vierkant
Author: Z.C. Fogarty
Author: B. Charbonneau
Author: M.S. Block
Author: P.D.P. Pharoah
Author: G. Chenevix-Trench
Author: M.A. Rossing
Author: D.W. Cramer
Author: C.L. Pearce
Author: J.M. Schildkraut
Author: U. Menon
Author: S.K. Kjaer
Author: D.A. Levine
Author: J. Gronwald
Author: H.A. Culver
Author: A.S. Whittemore
Author: B.Y. Karlan
Author: D. Lambrechts
Author: N. Wentzensen
Author: J. Kupryjanczyk
Author: J. Chang-Claude
Author: E.V. Bandera
Author: E. Hogdall
Author: F. Heitz
Author: S.B. Kaye
Author: P.A. Fasching
Author: I. Campbell
Author: M.T. Goodman
Author: T. Pejovic
Author: Y. Bean
Author: G. Lurie
Author: D. Eccles ORCID iD
Author: A. Hein
Author: M.W. Beckmann
Author: A.B. Ekici
Author: J. Paul
Author: R. Brown
Author: J.M. Flanagan
Author: P. Harter
Author: A. du Bois
Author: I. Schwaab
Author: C.K. Hogdall
Author: L. Lundvall
Author: S.H. Olson
Author: I. Orlow
Author: L.E. Paddock
Author: A. Rudolph
Author: U. Eilber
Author: A. Dansonka-Mieszkowska
Author: I.K. Rzepecka
Author: I. Ziolkowska-Seta
Author: L. Brinton
Author: H. Yang
Author: M. Garcia-Closas
Author: E. Despierre
Author: S. Lambrechts
Author: I. Vergote
Author: C. Walsh
Author: J. Lester
Author: W. Sieh
Author: V. McGuire
Author: J.H. Rothstein
Author: A. Ziogas
Author: J. Lubinski
Author: C. Cybulski
Author: J. Menkiszak
Author: A. Jensen
Author: S.A. Gayther
Author: S.J. Ramus
Author: A. Gentry-Maharaj
Author: A. Berchuck
Author: A.H. Wu
Author: M.C. Pike
Author: D. Van DenBerg
Author: K.L. Terry
Author: A.F. Vitonis
Author: J.A. Doherty
Author: S.E. Johnatty
Author: A. deFazio
Author: H. Song
Author: J. Tyrer
Author: T.A. Sellers
Author: C.M. Phelan
Author: K.R. Kalli
Author: J.M. Cunningham
Author: B.L. Fridley
Author: E.L. Goode

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×